STRUCTURE OF PDCD4, AN INHIBITOR OF THE RNA HELICASE EIF4A

Cornell University, Ithaca NY

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. PDCD4 (programmed Cell Death 4) is a newly discovered inhibitor of the eukaryotic translation initiation factor eIF4E. It inhibits the helicase activity of the factor, prevents RNA binding and has tumor suppressive activity. It consists of an N-terminal segment of unknown structure followed by two homologous MA3 domains. The structure of the C-terminal MA3 domain has been known. We were interested in the middle domain and in the mechanisms by which PDCD4 inhibits the RNA helicase. We solved the X-ray structure of the PDCD4 middle domain and characterized the binding interfaces of both MA3 domains with eIF4A.